Organocatalyzed Asymmetric Michael Addition of 3-Fluorooxindole to Vinylidene Bisphosphonates.

Both the 3-fluorooxindole and germinal bisphosphonate structural motifs are prevalent in bioactive molecules because of their associated biological activities. We describe an approach to accessing 3,3-disubstituted 3-fluorooxindoles bearing a geminal bisphosphate fragment through a highly enantioselective Michael addition reaction between 3-fluorooxindoles and vinylidene bisphosphonates. These reactions are catalyzed by a commercially available cinchona alkaloid catalyst, have a broad substrate scope concerning 3-fluorooxindoles, and provide the corresponding addition products in a yield of up to 95% with an enantiomeric excess of up to 95%. A reasonable reaction pathway to explain the observed stereochemistry is also proposed.

Association between the geriatric nutritional risk index and clinical outcomes among peritoneal dialysis patients: A meta-analysis.

BACKGROUND: To identify the relationship between the geriatric nutritional risk index (GNRI) and clinical outcomes in patients receiving peritoneal dialysis (PD). METHODS: The PubMed, EBASE, Web of Science and CNKI databases were searched for available studies up to December 25, 2023. The primary outcome was all-cause mortality, and the secondary outcomes included the incidence of PD dropout, major adverse cardiac and cerebrovascular events (MACCEs), technique failure and peritonitis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined to evaluate the predictive value of the GNRI for the occurrence of the above endpoints. RESULTS: Ten cohort studies with 3897 patients were included. The pooled results demonstrated that a lower GNRI was significantly associated with a greater incidence of all-cause mortality (HR = 0.71, 95% CI: 0.55-0.91; P = .007). In addition, a decreased GNRI predicted the occurrence of dropout from PD (HR = 0.971, 95% CI: 0.945-0.998, P = .034) and MACCE (HR = 0.95, 95% CI: 0.92-0.98, P = .001). However, no significant associations of the GNRI with technique failure (P = .167) or peritonitis (P = .96) were observed. CONCLUSION: A low GNRI is significantly associated with poor clinical outcomes and might serve as a novel and valuable prognostic indicator among PD patients.

Seed germination ecology of endangered plant Horsfieldia hainanensis Merr. In China.

BACKGROUND: Horsfieldia hainanensis Merr., an indicator species of China's humid tropical rainforests, is endangered due to difficulties with population regeneration. In this study, the biological characteristics and germination adaptability of the seeds were studied for the first time, in order to provide a basis for analyzing the causes of endangerment and strategies for the artificial cultivation of H. hainanensis. The effects of biological characteristics (population, arils, seed coat, seed weight, seed moisture content) and environmental factors (temperature, light, drought, substrate, burial depth) on seed germination and seedling growth of H. hainanensis were studied. RESULTS AND DISCUSSION: The fruits were found to be capsules containing seeds wrapped in a pericarp and fleshy aril, which provide protection and assist in seed dispersal, but also pose risks to the seeds, as the peel and fleshy aril can become moldy under high temperature and humidity conditions. There were significant differences in fruit morphology and germination characteristics among different populations, and the seed quality of populations in Niandian village, Daxin County, Chongzuo City, Guangxi Zhuang Autonomous Region was better. The arils significantly inhibited seed germination, the germination of large seeds was better, and seedling growth from medium seeds was superior. H. hainanensis seeds were sensitive to dehydration, and intolerant to drought and low temperature, which is typical of recalcitrant seeds. The seeds are suitable for germination on a moist substrate surface with good water retention and breathability at 30-35℃.

Iodine-induced synthetic method and pharmacokinetic study of cis- and trans-crocetin.

Objective: This experiment aimed to obtain the relatively rare cis-crocetin isomer from natural plants, which predominantly exist in the more stable all-trans configuration. This was achieved through iodine-induced isomerization, followed by purification and structural identification. The study also aimed to compare the pharmacokinetic differences between cis- and trans-crocetin in vivo. Methods: Trans-crocetin of high purity was extracted by hydrolysis from gardenia yellow pigment. Cis-crocetin was then synthesized through an optimized electrophilic addition reaction induced by elemental iodine, and subsequently separated and purified via silica gel column chromatography. Structural identification of cis-crocetin was determined using IR, UV, and NMR techniques. In vivo pharmacokinetic studies were conducted for both cis- and trans-crocetin. In addition to this, we have conducted a comparative study on the in vivo anti-hypoxic activity of trans- and cis-crocetin. Results: Under the selected reaction conditions using DMF as the solvent, with a concentration of 2.5 mg/mL for both trans-crocetin and the iodine solution, and adjusting the illumination time according to the amount of trans-crocetin, the rate of iodine-induced isomerization was the fastest. Cis-crocetin was successfully obtained and, after purification, its structure was identified and found to be consistent with reported data. Cis-crocetin exhibited a faster absorption rate and higher bioavailability, and despite its shorter half-life, it could partially convert to trans-crocetin in the body, thereby extending the duration of the drug's action within the body to some extent. Conclusion: This study accomplished the successful preparation and structural identification of cis-crocetin. Additionally, through pharmacokinetic studies, it uncovered notable variations in bioavailability between cis- and trans-crocetin. These findings serve as a solid scientific foundation for future functional research and practical applications in this field.

Impaired Relaxation in Induced Pluripotent Stem Cell-Derived Cardiomyocytes with Pathogenic TNNI3 Mutation of Pediatric Restrictive Cardiomyopathy.

BACKGROUND: Restrictive cardiomyopathy (RCM) is characterized by impaired diastolic function with preserved ventricular contraction. Several pathogenic variants in sarcomere genes, including TNNI3, are reported to cause Ca2+ hypersensitivity in cardiomyocytes in overexpression models; however, the pathophysiology of induced pluripotent stem cell (iPSC)-derived cardiomyocytes specific to a patient with RCM remains unknown. METHODS AND RESULTS: We established an iPSC line from a pediatric patient with RCM and a heterozygous TNNI3 missense variant, c.508C>T (p.Arg170Trp; R170W). We conducted genome editing via CRISPR/Cas9 technology to establish an isogenic correction line harboring wild type TNNI3 as well as a homozygous TNNI3-R170W. iPSCs were then differentiated to cardiomyocytes to compare their cellular physiological, structural, and transcriptomic features. Cardiomyocytes differentiated from heterozygous and homozygous TNNI3-R170W iPSC lines demonstrated impaired diastolic function in cell motion analyses as compared with that in cardiomyocytes derived from isogenic-corrected iPSCs and 3 independent healthy iPSC lines. The intracellular Ca2+ oscillation and immunocytochemistry of troponin I were not significantly affected in RCM-cardiomyocytes with either heterozygous or homozygous TNNI3-R170W. Electron microscopy showed that the myofibril and mitochondrial structures appeared to be unaffected. RNA sequencing revealed that pathways associated with cardiac muscle development and contraction, extracellular matrix-receptor interaction, and transforming growth factor-ß were altered in RCM-iPSC-derived cardiomyocytes. CONCLUSIONS: Patient-specific iPSC-derived cardiomyocytes could effectively represent the diastolic dysfunction of RCM. Myofibril structures including troponin I remained unaffected in the monolayer culture system, although gene expression profiles associated with cardiac muscle functions were altered.

Polyethylene Glycol Priming Enhances the Seed Germination and Seedling Growth of Scutellaria baicalensis Georgi under Salt Stress.

Seed priming has become a practical pre-sowing strategy to deal with abiotic stresses. This study aims to explore the effects of polyethylene glycol (PEG) priming on seed germination and seedling growth of Scutellaria baicalensis Georgi under salt stress. Regardless of seed priming, salt stress significantly inhibited the seed germination and seedling growth of S. baicalensis. PEG priming significantly alleviates the inhibitory effects of salt stress on seed germination and seedling growth when compared to non-priming and water priming. Among all treatments, PEG priming exhibited the highest germination rate, germination potential, seed vigor index, fresh weight, dry weight, and plant length; the highest contents of proline, soluble sugar, and soluble protein; the highest K+/Na+ ratio and relative water content; the highest antioxidant activities and contents; but the lowest H2O2, malondialdehyde (MDA) content, and relative electrical conductivity in response to salt stress. In addition, PEG priming had the highest transcript levels of antioxidant-related genes among all treatments under NaCl stress. Taken together, the results demonstrated that seed priming with PEG could be recommended as an effective practice to enhance the germination and early seedling growth of S. baicalensis under saline conditions.

Geniposide from Gardeniae Fructus exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The desiccative ripe fruits of Gardenia (Gardenia jasminoides Ellis) (called Zhizi in China) are known with cold character and the effects of reducing fire except vexed, clearing away heat evil, and cooling blood and eliminating stasis. Zhizi is often clinical formulated to treat various types of fever. Fever is a sign of inflammation and, geniposide from Zhizi has been proved with anti-inflammatory in various inflammatory models. AIM OF STUDY: The aim of this study was to investigate the antipyretic role of geniposide with three classical inflammatory fever models and explore the underlying mechanisms. MATERIALS AND METHODS: Water extract (WE), high polar part (HP), iridoid glycoside part (IG), and gardenia yellow pigment part (GYP) from Gardeniae Fructus (GF) were obtained from Zhizi. The antipyretic activities of these composes were tested with dry yeast induced fever rats. Geniposide was further purified from IG and the antipyretic activity was evaluated by gavage, intraperitoneal injection, and caudal intravenous injection to rats of fever induced by dry yeast, lipopolysaccharide (LPS), and 2, 4-dinitrophenol (DNP) in rats. Then, the mechanism of geniposide by intragastric administration was studied. The contents of thermoregulatory mediators and inflammatory factors relating to TLR4/NF-κB pathway in serum were determined by ELISA and Western blot, and the pathological changes of the hypothalamus were observed by HE staining. RESULTS: The temperature was decreased by geniposide in the three fever model rats. Geniposide can not only inhibit the increase of inflammatory factors in serum but also protect the hypothalamus from fever pathological damage in the three fever models. Western blot showed that geniposide could inhibit the TLR4/NF-κB pathway. CONCLUSION: Geniposide exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

A Promising New Model: Establishment of Patient-Derived Organoid Models Covering HPV-Related Cervical Pre-Cancerous Lesions and Their Cancers.

The lack of human-derived in vitro models that recapitulate cervical pre-cancerous lesions has been the bottleneck in researching human papillomavirus (HPV) infection-associated pre-cancerous lesions and cancers for a long time. Here, a long-term 3D organoid culture protocol for high-grade squamous intraepithelial lesions and cervical squamous cell carcinoma that stably recapitulates the two tissues of origin is described. Originating from human-derived samples, a small biobank of cervical pre-tumoroids and tumoroids that faithfully retains genomic and transcriptomic characteristics as well as the causative HPV genome is established. Cervical pre-tumoroids and tumoroids show differential responses to common chemotherapeutic agents and grow differently as xenografts in mice. By coculture organoid models with peripheral blood immune cells (PBMCs) stimulated by HPV antigenic peptides, it is illustrated that both organoid models respond differently to immunized PBMCs, supporting organoids as reliable and powerful tools for studying virus-specific T-cell responses and screening therapeutic HPV vaccines. In this study, a model of cervical pre-cancerous lesions containing HPV is established for the first time, overcoming the bottleneck of the current model of human cervical pre-cancerous lesions. This study establishes an experimental platform and biobanks for in vitro mechanistic research, therapeutic vaccine screening, and personalized treatment for HPV-related cervical diseases.

High-contrast multicolour photoswitching based on dithienylethene Schiff base with a hydrazinylquinoline moiety.

A new asymmetrical photochromic diarylethene DTE-HQo composed of a 2-hydrazinoquinoline moiety as the binding unit for ions and dithenylethene as a photoswitching trigger was reported. DTE-HQo displayed favourable photochromism upon irradiation with UV/vis light. Its fluorescent behaviour could be efficiently modulated by light, Zn2+, Cd2+ and HSO4-. The binding of Zn2+ induced a strong fluorescence peak at 510 nm in DTE-HQo due to the formation of a 1:2 complex [Zn2+ + 2DTE-HQo], resulting in a notable colour change from dark to intense white emission. Triggered by Cd2+, DTE-HQo formed a 1:1 complex [Cd2+ + DTE-HQo], leading to an enhanced emission intensity by 21-fold with an emission peak red-shifted from 461 nm to 514 nm. Unexpectedly, [Zn2+ + 2DTE-HQo] underwent hydrolysis when stimulated with water, generating a yellow-emitting complex [Zn2+ + DTE-HQo]. This color change easily distinguishes it from Cd2+ complex. Additionally, DTE-HQo showed high selectivity towards HSO4- and exhibited distinct "turn-on" fluorescence with a colour change from dark to bright blue upon stimulation. Moreover, the strong emission complexes of DTE-HQo with Zn2+, Cd2+ and HSO4- could be effectively quenched during the photocyclization process. Therefore, DTE-HQo can serve as an unimolecular multicolour photoswitching chemosensor, offering potential applications as a multifunctional probe for detecting Zn2+, Cd2+ and HSO4-.

Stem cells implanted with nanofibrous mats for injured endometrial regeneration and immune-microenvironment remodeling.

Severe endometrial injury caused by invasive uterine operation and/or endometritis often results in intrauterine adhesions (IUAs), which are named Asherman's syndrome (AS), further leading to menstrual disorders, infertility and severe complications during pregnancy and delivery. IUAs or AS has been a challenging medical problem. Stem cells are a promising therapeutic modality for endometrial regeneration in patients with refractory AS. Here, we developed a new system of adipose-derived mesenchymal stem cells (ADMSCs) implantation on silk fibroin/polycaprolactone (SF/PCL) electrospun nanofibers (ADMSCs-SF/PCL) and used it in the damaged endometrium of a rat model. After SF/PCL enhanced the proliferation of transplanted ADMSCs, the results showed that the ADMSCs-SF/PCL system could recover morphology, promote regeneration of the glands and angiogenesis by increasing CD31 expression, and reverse endometrial fibrosis by decreasing TGF-ß/Smad expression. In addition, the ADMSCs-SF/PCL system also increased the expression of differentiation and decidualization markers, including HOXA11, HAND2 and FOXO1. Most importantly, the ADMSCs-SF/PCL system could remodel the special immune microenvironment, resulting in dominant NK infiltration and a normal Th1/Th2 bias in the endometrium. Moreover, this treatment had a lower but more persistent effect than estrogen. Thus, the ADMSCs-SF/PCL system enhanced endometrial restoration, suggesting a promising strategy for damaged endometrial regeneration and immune microenvironment remodeling.

Effect of different hypoxic and hypobaric interventions on blood gas and erythrocyte-related indicators in rats. / ä¸åŒç¼ºæ°§å¹²é¢„å¯¹ä½ŽåŽ‹ä½Žæ°§æ¨¡åž‹é¼ è¡€æ°”åŠçº¢ç»†èƒžç›¸å ³æŒ‡æ ‡çš„å½±å“.

OBJECTIVES: To explore the effects of hypoxic and hypobaric conditions on blood gas and erythrocyte-related indicators in rats. METHODS: SD male rats were exposed to low-pressure hypoxic conditions simulating an altitude of 6500 m in a small or a large experimental cabin. Abdominal aortic blood samples were collected and blood gas indicators, red blood cells (RBCs) count, and hemoglobin (Hb) content were measured. The effects of exposure to different hypoxia times, different hypoxia modes, normal oxygen recovery after hypoxia, and re-hypoxia after hypoxia preconditioning on blood gas indicators, RBCs count and Hb content were investigated. RESULTS: The effect of blood gas indicators was correlated with the length of exposure time of hypoxia and the reoxygenation after leaving the cabin. Hypoxia caused acid-base imbalance and its severity was associated with the duration of hypoxia; hypoxia also led to an increase in RBCs count and Hb content, and the increase was also related to the time exposed to hypoxia. The effects of reoxygenation on acid-base imbalance in rats caged in a small animal cabin were more severe that those in a large experimental cabin. Acetazolamide alleviated the effects of reoxygenation after leaving the cabin. Different hypoxia modes and administration of acetazolamide had little effect on RBCs count and Hb content. Normal oxygen recovery can alleviate the reoxygenation and acid-base imbalance of hypoxic rats after leaving the cabin and improve the increase in red blood cell and hemoglobin content caused by hypoxia. The improvement of hypoxia preconditioning on post hypoxia reoxygenation is not significant, but it can alleviate the acid-base imbalance caused by hypoxia in rats and to some extent improve the increase in red blood cell and hemoglobin content caused by hypoxia. CONCLUSIONS: Due to excessive ventilation and elevated RBCs count and Hb content after hypoxia reoxygenation, oxygen partial pressure and other oxygenation indicators in hypoxic rats are prone to become abnormal, while blood gas acid-base balance indicators are relatively stable, which are more suitable for evaluating the degree of hypoxia injury and related pharmacological effects in rats.

LncBIRC3-OT promotes the malignant progression of glioma by interacting with RELA to upregulate stanniocalcin-1 expression.

Glioma is the most common malignant intracranial tumor, accounting for 80 % of all malignant brain tumors. Growing evidence suggests that lncRNAs are involved in the growth, angiogenesis, metastasis, and therapeutic resistance in a variety of tumors, including glioma. In this study, lncBIRC3-OT (NONHSAT159592.1), which is highly expressed in glioma, was screened by RNA-seq method and verified by quantitative reverse transcription polymerase chain reaction. Subsequently, we knocked down the endogenous expression of lncBIRC3-OT in U87 and U251 cells and found that down-regulated lncBIRC3-OT inhibited cell proliferation, colony formation, migration, and invasion. Mechanically, lncBIRC3-OT could guide RELA protein to the stanniocalcin-1 (STC1) promoter, initiate STC1 transcription, and ultimately promote the progression of glioma. Together, these findings suggest that lncBIRC3-OT is an important regulator promoting glioma progression, and may be a promising therapeutic target for glioma.

Isogenic pairs of induced-pluripotent stem-derived endothelial cells identify DYRK1A/PPARG/EGR1 pathway is responsible for Down syndrome-associated pulmonary hypertension.

Down syndrome (DS) is the most prevalent chromosomal disorder associated with a higher incidence of pulmonary arterial hypertension (PAH). The dysfunction of vascular endothelial cells (ECs) is known to cause pulmonary arterial remodeling in PAH, although the physiological characteristics of ECs harboring trisomy 21 (T21) are still unknown. In this study, we analyzed the human vascular ECs by utilizing the isogenic pairs of T21-induced pluripotent stem cells (iPSCs) and corrected disomy 21 (cDi21)-iPSCs. In T21-iPSC-derived ECs, apoptosis and mitochondrial reactive oxygen species (mROS) were significantly increased, and angiogenesis and oxygen consumption rate (OCR) were significantly impaired as compared with cDi21-iPSC-derived ECs. The RNA-sequencing identified that EGR1 on chromosome 5 was significantly upregulated in T21-ECs. Both EGR1 suppression by siRNA and pharmacological inhibitor could recover the apoptosis, mROS, angiogenesis, and OCR in T21-ECs. Alternately, the study also revealed that DYRK1A was responsible to increase EGR1 expression via PPARG suppression, and that chemical inhibition of DYRK1A could restore the apoptosis, mROS, angiogenesis, and OCR in T21-ECs. Finally, we demonstrated that EGR1 was significantly upregulated in the pulmonary arterial ECs from lung specimens of a patient with DS and PAH. In conclusion, DYRK1A/PPARG/EGR1 pathway could play a central role for the pulmonary EC functions and thus be associated with the pathogenesis of PAH in DS.

Ion-modulated interfacial fluorescence in droplet microfluidics using an ionophore-doped oil.

Fluorescence at the oil-water interface is used for chemical sensing in droplet microfluidics. Potassium ions in aqueous droplets are extracted into oil segments doped with an ionophore, a cation exchanger, and a cationic dye to expel the dye. When a low concentration of dye with a balanced solubility is used, it actively accumulates at the thin interface between oil and water instead of getting dissolved in the aqueous phase. The interfacial fluorescence is monitored distinct from the fluorescence in the oil sensor and the aqueous sample, allowing for highly sensitive and selective turn-on fluorescence sensing of ions.

AI-Based Optimal Treatment Strategy Selection for Female Infertility for First and Subsequent IVF-ET Cycles.

Over the last 20 years, China's infertility rate has risen from 3% to 12.5%-15%. Infertility has become the third largest disease following cancer and cardiovascular disease. Then, the in vitro fertilization and embryo transfer (IVF-ET) becomes more and more important in infertility treatment field. However, the reported success rate for IVT-ET is 30%-40% and costs are gradually rising. Meanwhile, to increase success rates and decrease costs, the optimal selection of the IVF-ET treatment strategy is crucial. In a clinical work, the IVF-ET treatment strategy selection is always based on the experience of the doctor without a uniform standard. To solve this important and complex problem, we proposed an artificial intelligence (AI)-based optimal treatment strategy selection system to extract implicit knowledge from clinical data for new and returning patients, by mimicking the IVF-ET process and analysing a myriad of treatment decisions. We demonstrated that the performance of the model was different in 10 AI classification algorithms. Hence, we need to select the optimal method for predicting patient pregnancy result in different IVF-ET treatment strategies. Moreover, feature ranking is determined in the proposed model to measure the importance of each patient characteristics. Therefore, better advice can be provided for individual patient characteristics, doctors can provide more valid suggestions regarding certain patient characteristics to improve the accuracy of diagnosis and efficiency.

Ultrasensitive Ionophore-Based Liquid Sensors for Colorimetric Ion Measurements in Blood.

The self-monitoring of electrolytes using a small volume of capillary blood is needed for the management of many chronic diseases. Herein, we report an ionophore-based colorimetric sensor for electrolyte measurements in a few microliters of blood. The sensor is a pipet microtip preloaded with a segment of oil (plasticizer) containing a pH-sensitive chromoionophore, a cation exchanger, and an ionophore. The analyte is extracted from the sample into the oil via a mixing protocol controlled by a stepper motor. The oil with an optimized ratio of sensing chemicals shows an unprecedentedly large color response for electrolytes in a very narrow concentration range that is clinically relevant. This ultrahigh sensitivity is based on an exhaustive response mode with a novel mechanism for defining the lower and higher limits of detection. Compared to previous optodes and molecular probes for ions, the proposed platform is especially suitable for at-home blood electrolyte measurements because (1) the oil sensor is interrogated independent of the sample and therefore works for whole blood without requiring plasma separation; (2) the sensor does not need individual calibration as the consistency between liquid sensors is high compared to solid sensors, such as ion-selective electrodes and optodes; and (3) the sensing system consisting of a disposable oil sensor, a programmed stepper motor, and a smartphone is portable, cost-effective, and user-friendly. The accuracy and precision of Ca2+ sensors are validated in 51 blood samples with varying concentrations of total plasma Ca2+. Oil sensors with an ultrasensitive response can also be obtained for other ions, such as K+.

Self-Calibrated Ion-Selective Electrodes.

Ion-selective electrode (ISE) potentiometry is reliable only if on-site calibration using a standard solution is performed before ion measurements. The complex device and operation required for calibration hinder the implementation of ISEs in decentralized sensing. Reported herein is a new type of ISE that is calibrated by a built-in component of the sensor without requiring any fluid handling processes. The indicator and reference electrodes are connected by a thin ionic conductor such as an aqueous phase containing the measuring ions in a capillary tube. This connection establishes a baseline electromotive force (EMF) that incorporates phase boundary potentials across multiple interfaces of the electrochemical cell and serves as a one-point calibration. Unlike conventional ISEs that rely on one EMF reading for each measurement, the proposed sensor utilizes a sample-induced EMF change relative to the baseline for each ion measurement. The variability in relative EMF is found to be <2.0 mV for multiple full potentiometric sensors consisting of plasticizer-based K+ ISEs and hydrogel-based Ag/AgCl reference electrodes. This value is significantly smaller than the variability of absolute EMF readouts in similar sensors without the self-calibration design. Moreover, when the ion-conducting calibration bridge has a low concentration of primary ions, low ion mobility, and/or a small contact area with the indicator and reference phases, it does not compromise the Nernstian response slope toward the analyte ions in the sample and therefore does not need to be removed for sample testing. The accuracy of the single-use self-calibrated K+ sensor in testing undiluted human blood samples is validated using a commercial blood gas analyzer as the reference method. Although this study focuses on disposable sensors consisting of tubes, the fluidics-free self-calibration strategy may be adapted to other sensor configurations such as planar sensors.

Efficacy and safety of Xian-Lian-Jie-Du optimization decoction as an adjuvant treatment for prevention of recurrence in patients with stage IIIB/IIIC colon cancer: study protocol for a multicentre, randomized controlled trial.

INTRODUCTION: Colon cancer remains one of the most prevalent cancers worldwide. Unfortunately, there are no recognized and effective therapeutic strategies to prevent tumor recurrence after radical resection and chemotherapy, and the disease-free survival (DFS) in patients with stage IIIB or IIIC disease remains unsatisfactory. Xian-Lian-Jie-Du optimization decoction (XLJDOD) is a Chinese herbal medicine (CHM) empirical prescription, which has been validated experimentally and clinically that could inhibit the progression of colorectal cancer and ameliorate the symptoms. The purpose of this study is to evaluate the efficacy and safety of XLJDOD in prevention of recurrence of colon cancer. METHODS: This study is a multi-center, double-blind, randomized, placebo-controlled trial conducted at 13 hospitals of China. Following the completion of surgery and adjuvant 5- fluorouracil-based chemotherapy, a total of 730 subjects with stage IIIB or IIIC colon cancer will be randomized in a 1:1 ratio to an intervention group (n = 365; XLJDOD compound granule) and a control group (n = 365; Placebo). Patients will receive 6-month treatments and be followed up with 3 monthly assessments for 2 years. The primary outcome is 2-year DFS rate and the secondary outcomes are 1, 2-year relapse rate (RR), overall survival (OS) and quality of life (QoL). Safety outcomes such as adverse events will be also assessed. A small number of subgroup analysis will be carried out to explore the heterogeneity of effects of XLJDOD. DISCUSSION: The outcomes from this randomized controlled trial will provide objective evidences to evaluate XLJDOD's role as an adjuvant treatment in colon cancer. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , identifier: NCT05709249. Registered on 31 Jan 2023.

Immunodiagnosis - the promise of personalized immunotherapy.

Immunotherapy showed remarkable efficacy in several cancer types. However, the majority of patients do not benefit from immunotherapy. Evaluating tumor heterogeneity and immune status before treatment is key to identifying patients that are more likely to respond to immunotherapy. Demographic characteristics (such as sex, age, and race), immune status, and specific biomarkers all contribute to response to immunotherapy. A comprehensive immunodiagnostic model integrating all these three dimensions by artificial intelligence would provide valuable information for predicting treatment response. Here, we coined the term "immunodiagnosis" to describe the blueprint of the immunodiagnostic model. We illustrated the features that should be included in immunodiagnostic model and the strategy of constructing the immunodiagnostic model. Lastly, we discussed the incorporation of this immunodiagnosis model in clinical practice in hopes of improving the prognosis of tumor immunotherapy.

Changes in Soil Properties, Microbial Quantity and Enzyme Activities in Four Castanopsis hystrix Forest Types in Subtropical China.

It is well established that forest type can have a profound impact on soil physicochemical properties but the associated changes in soil microbial communities and the mechanisms by which soil quality is improved by various plantations are not fully understood. In this study, soil physicochemical properties and microbial and enzyme activities were investigated in four forest types-Castanopsis hystrix pure forests (CHPF), C. hystrix-Pinus elliottii mixed forests (CHPEF), C. hystrix-Michelia macclurei mixed forests (CHMMF), and C. hystrix-Mytilaria laosensis mixed forests (CHMLF) in the subtropical region of China. The purpose of this study was to assess the effects of afforestation types on characteristics of soil-its physical, chemical, and biological properties. The results showed that the contents of soil total organic carbon (TOC), soil total nitrogen (TN), microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN) were significantly improved in both CHMMF and CHMLF mixed forest stands when compared to the CHPF pure stand. Soil enzyme activities were enhanced in the mixed forests. In particular, high phosphatase activity was observed in CHMLF stands, leading to the transformation of soil phosphorus to available phosphorus in this forest type. Our study demonstrated that the broad-leaved mixed forests, but not coniferous mixed forests, could significantly improve soil quality in the study region. Our research provides a scientific insight into the promotion of vegetation restoration and plantation forest management in plantation regions of subtropical areas.